Andrew M. Kates

Impact of aging on substrate metabolism by the human heart.

BACKGROUND Results of studies in experimental animals have shown that, with age, myocardial fatty acid metabolism decreases, and glucose metabolism increases. Whether similar changes occur in humans is unknown. METHODS Seventeen healthy younger normal volunteers (six males, 26 +/- 5 years) and 19 healthy older volunteers (nine males, 67 +/- 5 years) underwent positron emission tomography (PET) under resting conditions in the fasted state. Myocardial blood flow (MBF), myocardial oxygen consumption (MVO(2)), myocardial fatty acid utilization (MFAU) and oxidation (MFAO), and myocardial glucose utilization (MGU) were quantified by PET with (15)O-water, (11)C-acetate, (11)C-palmitate, and(11)C-glucose, respectively. RESULTS Although MBF was similar between the groups, MVO(2) was higher in the older subjects (5.6 +/- 1.6 micromol/g/min) compared with younger subjects (4.6 +/- 1.0 micromol/g/min, p < 0.04). Rates of MFAU and MFAO (corrected for MVO(2)) were significantly lower in older subjects than in younger subjects (MFAU/MVO(2): 35 +/- 10 vs. 51 +/- 20 nmol free fatty acids (FFA)/nmol O(2) x 10(-3), p < 0.005, and MFAO/MVO(2): 33 +/- 10 vs. 48 +/- 18 nmol FFA/nmol O(2) x 10(-3), p < 0.004). In contrast, the rates of MGU corrected for MVO(2) did not differ between the groups. CONCLUSIONS With aging, humans exhibit a decline in MFAU and MFAO. Although absolute rates of MGU do not increase, by virtue of the decline in MFAU there is likely an increase in relative contribution of MGU to substrate metabolism. The clinical significance of this metabolic switch awaits further study.

Challenges facing early career academic cardiologists

Early career academic cardiologists currently face unprecedented challenges that threaten a highly valued career path. A team consisting of early career professionals and senior leadership members of American College of Cardiology completed this white paper to inform the cardiovascular medicine profession regarding the plight of early career cardiologists and to suggest possible solutions. This paper includes: 1) definition of categories of early career academic cardiologists; 2) general challenges to all categories and specific challenges to each category; 3) obstacles as identified by a survey of current early career members of the American College of Cardiology; 4) major reasons for the failure of physician-scientists to receive funding from National Institute of Health/National Heart Lung and Blood Institute career development grants; 5) potential solutions; and 6) a call to action with specific recommendations.

Possible Paradoxical Embolism as a Rare Cause for an Acute Myocardial Infarction

Paradoxical embolus is a rare entity and it has been incriminated as a cause of both cryptogenic strokes and myocardial infarctions (MI). Herein, we present a case of a patient diagnosed with a pulmonary embolism 1 week prior who now presented with an acute MI. Subsequent evaluation revealed a patent foramen ovale and a large thrombus in the right pulmonary artery. It was presumed that the etiology of her infarct was due to paradoxical embolus. The management of the patient is discussed and the literature is reviewed.

National Institutes of Health Career Development Awards for Cardiovascular Physician-Scientists: Recent Trends and Strategies for Success.

Nurturing the development of cardiovascular physician-scientist investigators is critical for sustained progress in cardiovascular science and improving human health. The transition from an inexperienced trainee to an independent physician-scientist is a multifaceted process requiring a sustained commitment from the trainee, mentors, and institution. A cornerstone of this training process is a career development (K) award from the National Institutes of Health (NIH). These awards generally require 75% of the awardees professional effort devoted to research aims and diverse career development activities carried out in a mentored environment over a 5-year period. We report on recent success rates for obtaining NIH K awards, provide strategies for preparing a successful application and navigating the early career period for aspiring cardiovascular investigators, and offer cardiovascular division leadership perspectives regarding K awards in the current era. Our objective is to offer practical advice that will equip trainees considering an investigator path for success.

Bicuspid aortic valves and thoracic aortic aneurysms in patients with intracranial aneurysms

Objective: The purpose of this study was to determine the prevalence of bicuspid aortic valves (BAVs) and thoracic ascending aortic aneurysms (TAAs) in a retrospective cohort of patients treated for intracranial aneurysms (IAs). Methods: Patients treated for IA at our institution between 2002 and 2011 were identified and their clinical records reviewed. Those without an echocardiogram of sufficient quality to assess the aortic valve were excluded. The prevalence of BAVs and TAAs in this remaining cohort was determined based on echocardiography reports, medical records, and cross-sectional chest imaging. Results: Of 1,047 patients, 317 had adequate echocardiography for assessment of BAV. Of these, 82 also had cross-sectional chest imaging. Of the 317 patients, 2 had BAV and 15 had TAA. The prevalence of BAVs (0.6%, 95% confidence interval 0.2%–2.2%) was similar to population prevalence estimates for this condition; however, the prevalence of TAAs (4.7%, 95% confidence interval 2.9%–7.6%) was larger than expected in a normal age- and sex-matched population. Conclusions: Our data demonstrate an association between IA and TAA, but not independently for BAV.

Noninvasive coronary artery imaging in the diagnosis and management of patients with ischemic heart disease.

The inherent limitations of x-ray coronary angiography have led to the development for both noninvasive and minimally invasive techniques for imaging the coronary arteries to assist in the diagnosis and management of patients with ischemic heart disease. Significant advances in transesophageal echocardiography, electron beam computed tomography, and magnetic resonance imaging now permit imaging of the proximal to mid-coronary arteries. Moreover, results of initial studies demonstrate the promise of these methods to detect coronary artery stenoses. In addition, each of these methods provides biochemical or physiologic data about the stenoses that are not obtainable through x-ray angiography. Quantification of coronary calcification via electron beam computed tomography has shown promise as a surrogate marker of coronary atherosclerosis. Transesophageal echocardiography and magnetic resonance imaging appear useful in evaluating the physiologic significance of angiographically detectable coronary artery stenoses via assessment of coronary blood flow. However, it should be noted that significant improvements in technology or acquisition parameters must occur before these techniques can be used on a routine clinical basis for coronary artery imaging. The relative merits and ultimate clinical potential of each of these techniques are discussed in this article.

The cardiovascular in-training examination: development, implementation, results, and future directions.

BACKGROUND The American College of Cardiology (ACC), in collaboration with the National Board of Medical Examiners (NBME), developed the first standardized in-training examination (ITE) for cardiovascular disease fellows-in-training (FITs). In addition to testing knowledge, this examination uses the newly developed ACC Curricular Milestones to provide specific, competency-based feedback to program directors and FITs. The ACC ITE has been administered more than 5,000 times since 2011. OBJECTIVES This analysis sought to report the initial experience with the ITE, including feasibility and reliability of test development and implementation, as well as the ability of this process to provide useful feedback in key content areas. METHODS The annual ACC ITE has been available to cardiovascular disease fellowship programs in the United States since 2011. Questions for this Web-based, secure, multiple-choice examination were developed by a group of cardiovascular disease specialists and each question was analyzed by the NBME to ensure quality. Scores were equated and standardized to allow for comparability. Trainees and program directors were provided detailed feedback, including a list of the curricular competencies tested by those questions answered incorrectly. RESULTS The ITE was administered 5,118 times. In 2013, the examination was taken by 1,969 fellows, representing 194 training programs. Among the 3 training years, there was consistency in the examination scores. Total test scores and scores within each of the content areas increased with each FIT year (there was a statistically significant difference in each cohorts average scale score across administration years). There was also significant improvement in examination scores across the fellowship years. CONCLUSIONS The ACC ITE is a powerful tool available to all training programs to assess medical knowledge. This examination also delivers robust and timely feedback addressing individual knowledge gaps, and thus, may serve as a basis for improving training curricula.

Role of New Drugs for Management of Atrial Fibrillation

Objective: To evaluate the role of newer agents in the management of atrial fibrillation (AF). Data Sources: EMBASE and MEDLINE were searched (up to June 2012) combining medication names with atrial fibrillation, humans, clinical trials, and pharmacoeconomic. References of the articles identified and www.clinicaltrials.gov were also reviewed. Study Selection and Data Extraction: Studies were limited to the English language with clinical or pharmacoeconomic end points followed by the consensus of 3 authors. Data Synthesis: Formulated to reduce some of the adverse effects associated with amiodarone by removing the iodine component, dronedarone has improved clinical outcomes over placebo when used in paroxysmal or persistent AF; however, it is less efficacious than amiodarone. Worse outcomes with dronedarone have been seen in patients with heart failure or permanent AF. It has not been compared to antiarrhythmic agents other than amiodarone, and pharmacoeconomic evaluations are lacking. Dabigatran 150 mg is superior to warfarin in preventing stroke or systemic embolism and has been associated with lower rates of vascular-associated mortality. Although the rates of major bleeding were not significantly different between the 2 agents, gastrointestinal bleeding and myocardial infarction occurred more frequently with dabigatran. Dabigatran appears to have the most pharmacoeconomic benefit over warfarin in patients with a higher risk of stroke. Rivaroxaban is noninferior to warfarin for the prevention of stroke and systemic embolism, with no difference in the rates of major bleeding. Cost-effectiveness studies have not been performed with this agent at this time. In patients with AF who were not suitable candidates for warfarin, apixaban is superior to aspirin in preventing stroke or systemic embolism without increasing the risk for major bleeding. Additionally, apixaban is superior to warfarin in preventing stroke or systemic embolism, results in fewer bleeding events, and is associated with lower mortality. Apixaban is not cost-effective against aspirin when used for a short duration but gains superiority with prolonged use or in patients with higher risks of stroke. Additionally, apixaban appears to offer a pharmacoeconomic advantage over warfarin at no to minimal cost. Each new anticoagulant lacks a reversal agent and an assay to detect the presence of the anticoagulant, as well as long-term data when used in the clinical setting. Conclusions: Use of dronedarone should be limited to patients with paroxysmal or persistent AF and should not be used in patients with heart failure or with permanent AF. Newer antithrombotic agents appear to be promising alternatives for the prevention of stroke in patients with AF; however, more data are needed to understand their role.

Highlights of the American College of Cardiology Annual Scientific Sessions 2017

Recently, the 66th Annual American College of Cardiology (ACC) Scientific Sessions convened in Washington, DC, building on the theme of “more learning, less lecturing”. Despite the challenge of winter storm Stella, the meeting went off without a hitch, bringing together more than 18 500 attendees from across the world. Clinical science was at the forefront of the meeting, with 23 late-breaking clinical trials and 17 featured clinical research presentations. In addition, ACC.17 (2017 American College of Cardiology Annual Scientific Sessions) offered an updated core curriculum program, half-day intensive sessions focusing on palliative care, healthcare equity, and faculty development, live case demonstrations, and a personalized skills center, featuring hands-on simulation and test question review. Audience participation and response were featured throughout the meeting. New this year, physician attendees received simultaneous credit for continuing medical education and American Board of Internal Medicine Maintenance of Certification (ABIM-MOC) for the majority of the educational sessions; European physicians received external continuing medical education credit; and pharmacists and nurses received continuing education credits. The opening session featured Richard Chazal, MACC, ACC President, and this year’s Simon Dack Lecturer, David Skorton, FACC, Secretary of the Smithsonian Institute. Dr Chazal remarked on the ever-changing landscape of cardiovascular medicine, while Dr Skorton emphasized the importance and richness of the arts and humanities in our profession and our lives. Thereafter, 3 late-breaking clinical trials were presented, setting the stage for an exciting display of practice-changing science. The FOURIER trial (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated …